Tumor necrosis factor receptor superfamily member 6 (FAS)

The protein contains 335 amino acids for an estimated molecular weight of 37732 Da.

 

Receptor for TNFSF6/FASLG. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. FAS-mediated apoptosis may have a role in the induction of peripheral tolerance, in the antigen-stimulated suicide of mature T-cells, or both. The secreted isoforms 2 to 6 block apoptosis (in vitro). (updated: April 1, 2015)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  3. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 100%
Model score: 100
No model available.

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VariantDescription
dbSNP:rs3218619
non-Hodgkin lymphoma
ALPS1A; associated with autoimmune hepatitis type 2
ALPS1A
squamous cell carcinoma
ALPS1A
dbSNP:rs3218614
squamous cell carcinoma
non-Hodgkin lymphoma; somatic mutation
non-Hodgkin lymphoma
dbSNP:rs28362322
non-Hodgkin lymphoma; somatic mutation
ALPS1A
ALPS1A
ALPS1A
ALPS1A
ALPS1A
ALPS1A; no effect on interaction with FADD
ALPS1A
ALPS1A
squamous cell carcinoma
ALPS1A; loss of interaction with FADD
ALPS1A
ALPS1A
ALPS1A
ALPS1A
ALPS1A
non-Hodgkin lymphoma; somatic mutation
ALPS1A
ALPS1A; loss of interaction with FADD
ALPS1A
ALPS1A; also found in non-Hodgkin lymphoma; somatic mutation; loss of interaction with FADD
non-Hodgkin lymphoma; somatic mutation
non-Hodgkin lymphoma; somatic mutation
dbSNP:rs3218611
ALPS1A

Biological Process

Activation of cysteine-type endopeptidase activity involved in apoptotic process GO Logo
Activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO Logo
Activation-induced cell death of T cells GO Logo
Apoptotic process GO Logo
Apoptotic signaling pathway GO Logo
B cell mediated immunity GO Logo
Cellular response to amino acid starvation GO Logo
Cellular response to hyperoxia GO Logo
Cellular response to lithium ion GO Logo
Cellular response to mechanical stimulus GO Logo
Circadian rhythm GO Logo
Extrinsic apoptotic signaling pathway GO Logo
Extrinsic apoptotic signaling pathway in absence of ligand GO Logo
Extrinsic apoptotic signaling pathway via death domain receptors GO Logo
Fas signaling pathway GO Logo
Gene expression GO Logo
Hepatocyte apoptotic process GO Logo
Immune response GO Logo
Immunoglobulin production GO Logo
Inflammatory cell apoptotic process GO Logo
Inflammatory response GO Logo
Motor neuron apoptotic process GO Logo
Multicellular organism development GO Logo
Necroptotic signaling pathway GO Logo
Negative regulation of apoptotic process GO Logo
Negative regulation of B cell activation GO Logo
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO Logo
Negative thymic T cell selection GO Logo
Obsolete transformed cell apoptotic process GO Logo
Positive regulation of apoptotic process GO Logo
Positive regulation of apoptotic signaling pathway GO Logo
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO Logo
Positive regulation of extrinsic apoptotic signaling pathway in absence of ligand GO Logo
Positive regulation of protein homooligomerization GO Logo
Positive regulation of protein phosphorylation GO Logo
Protein complex assembly GO Logo
Protein homooligomerization GO Logo
Protein-containing complex assembly GO Logo
Regulation of apoptotic process GO Logo
Regulation of cell population proliferation GO Logo
Regulation of extrinsic apoptotic signaling pathway in absence of ligand GO Logo
Regulation of extrinsic apoptotic signaling pathway via death domain receptors GO Logo
Regulation of lymphocyte differentiation GO Logo
Regulation of myeloid cell differentiation GO Logo
Regulation of stress-activated MAPK cascade GO Logo
Renal system process GO Logo
Response to glucocorticoid GO Logo
Response to lipopolysaccharide GO Logo
Response to toxic substance GO Logo
Signal transduction GO Logo
Spleen development GO Logo

The reference OMIM entry for this protein is 134637

Fas cell surface death receptor; fas
Tumor necrosis factor receptor superfamily, member 6; tnfrsf6
Apoptosis antigen 1; apt1
Fas antigen
Surface antigen apo1; apo1
Cd95

CLONING

Itoh et al. (1991) isolated cDNAs encoding the human FAS antigen from a human T-cell lymphoma cDNA library. Sequence analysis predicted a 16-amino acid signal sequence followed by a mature protein of 319 amino acids with a single transmembrane domain and a molecular mass of approximately 36 kD. The FAS antigen shows structural homology with a number of cell surface receptors, including tumor necrosis factor (TNF) receptors (191190, 191191) and the low-affinity nerve growth factor receptor (NGFR; 162010). Northern blot analysis detected 2.7- and 1.9-kb FAS mRNAs in thymus, liver, ovary, and heart. Functional expression studies in mouse cells showed that the FAS antigen induced antibody-triggered apoptosis. Watanabe-Fukunaga et al. (1992) isolated mouse Fas antigen from a murine macrophage cDNA library. The deduced 306-amino acid sequence shares 49.3% sequence identity with the human sequence. Northern blot analysis detected a 2.1-kb Fas antigen mRNA in mouse thymus, heart, liver, and ovary. Oehm et al. (1992) demonstrated that the 48-kD APO1 antigen, defined by the mouse monoclonal antibody anti-APO1, is the same as the FAS antigen. APO1 was expressed on the cell surface of various normal and malignant cells, including activated human T and B lymphocytes and a variety of malignant human lymphoid cell lines, and binding of anti-APO1 antibody to the APO1 antigen induced apoptosis. - Antisense Transcript SAF Yan et al. (2005) described a novel RNA transcribed from the opposite strand of intron 1 of the human FAS gene, which they named SAF. The 1.5-kb transcript was expressed in human heart, placenta, liver, muscle, and pancreas, as well as in several cancer cell lines. SAF-transfected Jurkat cells were highly resistant to FAS-mediated but not to TNF-alpha (191160)-mediated apoptosis, compared to control transfectants. Although the overall mRNA expression level of FAS was not affected, expression of some novel forms of FAS transcripts was increased in SAF-transfected cells. Yan et al. (2005) hypothesized that SAF may protect T lymphocytes from FAS-mediated apoptosis by blocking the binding of FASL or its agonistic FAS antibody, and that SAF may regulate expression of FAS alternative splice forms through pre-mRNA processing.

GENE STRUCTURE

Yan et al. (2005) noted that the TNFRSF6 gene contains 9 exons. They identified an antisense transcript SAF within the 12.1-kb intron 1 that is transcribed in the opposite direction as the TNFRSF6 gene.

MAPPING

Inazawa et al. (1992) mapped the human FAS gene to chromosome 10q24.1 by fluorescence in situ hybridization. Using cosmid DNA containing the FAS gene as a probe for fluorescence in situ hybridization, Lichter et al. (1992) mapped the FAS gene to a subregion of chromosomal band 10q23; the analysis showed that the FAS gene is located just distal to the central part of band 10q23. Watanabe-Fukunaga et al. (1992) mapped the mouse Fas gene to the distal region of chromosome 19.

GENE FUNCTION

Talal (1994) used the term 'autogene,' a neologism, to refer to a gene whose abnormal function contributes to the development of autoimmune disease; the term is parallel to the term oncogene and the role of its product in malignancy. Mountz and Talal (1993) suggested that FAS is the first known autogene. Dhein et al. (1995) found that T-cell receptor-induced apoptosis was mediated by an APO1 ligand and APO1 in vitro. Apoptosis was significantly reduced by inhibition ... More on the omim web site

Subscribe to this protein entry history

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 134637 was added.